Editor’s quiz: GI snapshot

Gut: first published as 10.1136/gutjnl-2024-332234 on 22 March 2024. Downloaded from http://gut.bmj.com/ on March 27, 2024 at Serials Department University Library. Protected by
Unusual cause of rectal bleeding
in a patient with schizophrenia
CLINICAL PRESENTATION
A gentleman in his early 40s with a background of schizo-
phrenia on clozapine presented with a 2-­month history of rectal
bleeding, diarrhoea, weight loss, a microcytic anaemia and a
quantitative faecal immunochemical test (qFIT) result >400 µg
Hb/g. Colonoscopy demonstrated multiple large polypoid
lesions in the rectum and in the sigmoid colon; the sigmoid was
unable to be passed by the colonoscope due to narrowing of the
lumen (figure 1). Prior to histology being reported, CT colo-
nography was performed to further assess the colon. It reported
four malignant-­appearing lesions in the rectum and sigmoid with
suspicious sigmoid and retroperitoneal lymph nodes (figure 2).

QUESTION
What is the diagnosis?

ANSWER
Histology reported Michaelis-­ Gutmann bodies, diagnostic of
colonic malakoplakia (figure 3). Malakoplakia is a granuloma-
tous condition associated with immunosuppression which may
present with nodules, polyps or masses at colonoscopy. Esch-
erichia coli is the most commonly implicated organism.1 Our
patient was commenced on a 6-­month course of co-­trimoxazole
960 mg twice daily.
Figure 2 CT colonography: (A) axial image from involved
sigmoid colon in the pelvis, showing segment of abnormal nodular
circumferential thickening; (B) virtual endoscopy image from an involved
segment of sigmoid colon; (C) virtual barium enema image, derived from
CT colonography, which demonstrates multiple nodular filling defects
in the sigmoid colon, with the arrow pointing to a confluent stricturing
area in the proximal sigmoid.

He had no history of immunosuppression and bloodborne virus
screen was negative. Hypogammaglobulinaemia, however, was
demonstrated: IgG 2.69 g/L (7.0–19.0 g/L), IgA 0.32 g/L (0.90–4.5
g/L), IgM 0.15 g/L (0.45–1.80 g/L), with evidence of poor antibody
response to pneumococcal vaccination and normal B/T-­cell subset
counts, consistent with antibody deficiency (likely secondary to
clozapine). There was no clinical history of recurrent infections.
copyright.
Seven months post index colonoscopy, a repeat colonoscopy
showed significantly improved appearances (figure 4); there were
no pathognomonic features of malakoplakia on histology. He had
improved clinically and had gained 3 kg in weight.
Despite such improvements, adherence to co-­trimoxazole was
poor. His clozapine level 6 months prior to index colonoscopy was
0.66 mg/L (0.35–0.60 mg/L); this fell to 0.26 mg/L 6 months post
index colonoscopy. The dose remained 475 mg daily throughout.
Clozapine has been implicated in secondary hypogammaglobuli-
naemia,2–4 which has itself been reported in cases of malakoplakia5;

Figure 1 Index colonoscopy demonstrating multiple erythematous

polypoid lesions causing congestion and narrowing of the lumen
throughout the sigmoid colon and rectum: (A) proximal sigmoid (white Figure 3 Biopsies from the mid-­sigmoid (H&E, 400×), which show a
light endoscopy (WLE)), (B) distal sigmoid (WLE), (C) distal sigmoid diffuse histiocytic infiltrate in the lamina propria, containing Michaelis-­
(WLE) and (D) rectum (narrow-­band imaging). Gutmann bodies (arrows).
Grant RK, et al. Gut Month 2024 Vol 0 No 0    1
 Editor’s quiz: GI snapshot
Figure 4 Follow-­up colonoscopy demonstrating improved endoscopic
appearances throughout the sigmoid colon and rectum with reduction
in erythema and regression of polypoid masses: (A) proximal sigmoid
(WLE), (B) distal sigmoid (WLE), (C) distal sigmoid (WLE) and (D) rectum
(WLE). WLE, white light endoscopy.
however, the extent to which clozapine may have contributed to
this unusual presentation is uncertain.
Rebecca K Grant ‍ ‍,1,2 Charu Chopra ‍ ‍,3 Pujit Gandhi,4
Natarajan Manimaran,5 Jonathan T Serhan,6 Kate L Struthers,7
William M Brindle ‍ ‍8
1
Gastrointestinal Unit, Western General Hospital, NHS Lothian, Edinburgh, UK
2
The Centre for Liver and Digestive Disorders, Royal Infirmary of Edinburgh, NHS
Lothian, Edinburgh, UK
3
Department of Immunology, NHS Lothian, Edinburgh, UK
4
Department of General Adult Psychiatry, Stratheden Hospital, NHS Fife, Cupar, UK
5
Department of Colorectal Surgery, Victoria Hospital, NHS Fife, Kirkcaldy, UK
6
Department of Clinical Radiology, Victoria Hospital, NHS Fife, Kirkcaldy, UK
7
Department of Cellular Pathology, Victoria Hospital, NHS Fife, Kirkcaldy, UK
8
Department of Gastroenterology, Victoria Hospital, NHS Fife, Kirkcaldy, UK
Correspondence to Dr Rebecca K Grant, Gastrointestinal Unit, Western General
Hospital, NHS Lothian, Edinburgh EH4 2XU, UK; ​rebecca.​grant9@​nhs.​scot
Twitter Rebecca K Grant @rebeccakg6 and Charu Chopra @_DrCharu
Acknowledgements Many thanks to Mrs Paulina Marchewka (Clinical
Pharmacist, Royal Edinburgh Hospital, Edinburgh), Dr Pauline McConville (Consultant
2 Grant RK, et al. Gut Month 2024 Vol 0 No 0
Gut: first published as 10.1136/gutjnl-2024-332234 on 22 March 2024. Downloaded from http://gut.bmj.com/ on March 27, 2024 at Serials Department University Library. Protected by
Psychiatrist, Western General Hospital, Edinburgh), Dr Mark O’Connor (Specialty
Doctor in General Adult Community Psychiatry, Cambridge Street House, Edinburgh)
and Dr Ian Arnott (Consultant Gastroenterologist, Western General Hospital,
Edinburgh) for their advice and encouragement. Thank you also to Dr Katharine
Pollock (Consultant Gastroenterologist, Victoria Hospital, Kirkcaldy) for her assistance
in obtaining follow-­up colonoscopy images.
Contributors RKG drafted the original manuscript. CC, PG and NM critically
revised the manuscript. JTS provided the radiological images and interpretations.
KLS provided the histological image and interpretation. WMB was the senior author
and revised the manuscript for important intellectual content. RKG and WMB are the
guarantors of this work.
Funding The authors have not declared a specific grant for this research from any
funding agency in the public, commercial or not-­for-­profit sectors.
Competing interests None declared.
Patient consent for publication Not applicable.
Ethics approval In accordance with NHS Health Research Authority guidelines,
specific ethical review and approval were not considered necessary as this is a
retrospective case report using data already obtained as part of regular clinical care.
Provenance and peer review Not commissioned; externally peer reviewed.
© Author(s) (or their employer(s)) 2024. No commercial re-­use. See rights and
permissions. Published by BMJ.
To cite Grant RK, Chopra C, Gandhi P, et al. Gut Epub ahead of print: [please include
Day Month Year]. doi:10.1136/gutjnl-2024-332234
Received 17 February 2024
Accepted 17 March 2024
Gut 2024;0:1–2. doi:10.1136/gutjnl-2024-332234
ORCID iDs
copyright.
Rebecca K Grant http://orcid.org/0000-0002-9440-1192
Charu Chopra http://orcid.org/0000-0003-3798-3605
William M Brindle http://orcid.org/0000-0002-8972-0332
REFERENCES
1 Lee M, Ko HM, Rubino A, et al. Malakoplakia of the gastrointestinal tract:
clinicopathologic analysis of 23 cases. Diagn Pathol 2020;15:97.
2 Ponsford M, Castle D, Tahir T, et al. Clozapine is associated with secondary antibody
deficiency. Br J Psychiatry 2018;214:1–7.
3 Ponsford MJ, Pecoraro A, Jolles S. Clozapine-­associated secondary antibody deficiency.
Curr Opin Allergy Clin Immunol 2019;19:553–62.
4 Elkhalifa S, Garcez T, Drinkwater S, et al. First case series of clozapine induced
hypogammaglobulinaemia in England. Ann Psychiatry Treatm 2021;5:015–8.
5 Thorlacius H, Jerkeman A, Marginean FE, et al. Colorectal malakoplakia in a patient
with hypogammaglobulinemia. Gastrointest Endosc 2018;88:563–5.